This proposal is designed to examine recovery of function after damage to the adult nervous system, using the sympathetic innervation of the rat pineal gland as a model system. The pineal gland is innervated by both superior cervical ganglia, and this innervation can be reproducibly denervated or decentralized, either totally or partially. In addition, the activity of the pineal enzyme serotonin N-acetyltransferase (NAT) is highly dependent on sympathetic nerve stimulation and can be used as an index of the recovery of synaptic transmission. The pineal gland thus offers a number of experimental advantages for studying neural plasticity; however, we believe that the results obtained will be relevant to other sympathetic pathways and to other parts of the nervous system. The aim of this research will be not only to elucidate the anatomical and biochemical changes which arise in response to neural damage (for example, collateral sprouting, postjunctional supersensitivity, and regeneration) but also to assess the extent to which these changes restore or inhibit normal function. Five main areas will be emphasized: (1) the extent of recovery of pineal function after unilateral and after bilateral denervation, (2) the mechanisms involved in promoting and limiting recovery of function in these two cases, (3) the factors regulating collateral sprouting after unilateral denervation and the functional consequences of this sprouting, (4) the extent to which sympathetic neurons reinnervate their original target neurons after axotomy, and (5) the possible regulation of norepinephrine uptake sites in normal animals. A variety of anatomical, physiological, and biochemical techniques will be used including retrograde "double- labeling" of neuronal cell bodies, visualization of catecholamine varicosities using the glyoxylic acid method, direct electrical stimulation of specific sympathetic nerve trunks, and measurements of NAT, melatonin, and cAMP levels. These studies are designed to increase our knowledge of the basic mechanisms underlying plasticity in the adult nervous system. As such, they will be relevant to our understanding of factors promoting and limiting the recovery of function after neural damage, such as that caused by stroke, trauma, and degenerative neurological disease.